Trial reportThe Journal of allergy and clinical immunology2014
Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels.
Trial report in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- PGM3 insufficiency: a glycosylation disorder causing a notable T cell defect.Frontiers in immunology · 2024Pooled it
- Cross-talk between glycosylation pathways: Mechanistic insights and implications for human diseases.Molecular metabolism · 2026Review
- Oncostatin M receptor deficiency as a novel candidate genetic cause of autosomal recessive hyper-IgE syndrome.Journal of human immunity · 2026Article
- PSMD11 stabilizes PGM3 by antagonizing Parkin to promote bladder cancer progression through energy metabolism reprogramming.Cell death & disease · 2026Article
- A Novel Phosphoglucomutase-3 Gene Variant Causing Milder Phenotype in Two Families.Journal of clinical immunology · 2026Article
- Endocrine Implications of Congenital Disorders of GlycosylationJournal of clinical research in pediatric endocrinology · 2026Review
- Transcriptomic Adjustment to Decreasing Oxygen Reveals Novel Functional Strategies for Extreme Hypoxia Tolerance in the Copepod Tigriopus californicus.Genome biology and evolution · 2026Article
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- Pulmonary features and stage of disease in adult patients with hyper-IgE syndrome: a single-centre clinical study and literature review.Orphanet journal of rare diseases · 2025Article
- Persistent Neutropenia and Atopy in an Adolescent: A Subtle Presentation of Phosphoglucomutase 3 Deficiency.Cureus · 2025Article
- Hyper IgE Syndrome: Bridging the Gap Between Immunodeficiency, Atopy, and Allergic Diseases.Current allergy and asthma reports · 2025Review
- Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review.Health science reports · 2025Article
- Inborn Errors of Immunity Presenting with Early-Onset Severe Atopy.Medicina (Kaunas, Lithuania) · 2025Review
- Understanding and Managing Hyper IgE Syndromes.ImmunoTargets and therapy · 2025Review
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders.Life (Basel, Switzerland) · 2024Review
- Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.Science immunology · 2024Article
- TThe Journal of allergy and clinical immunology · 2024Review
- Flow cytometry-based diagnostic approach for inborn errors of immunity: experience from Algeria.Frontiers in immunology · 2024Article
- Revisiting the immunopathology of congenital disorders of glycosylation: an updated review.Frontiers in immunology · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
45 authors at 15 institutions in 7 countries.
Funding
Abstract
backgroundRecurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans.
objectiveWe sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8.
methodsAfter establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry.
resultsMutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation.
conclusionImpairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.